Advances in Solubility Enhancement Techniques

Solubility, the phenomenon of dissolution of solute in solvent to give a homogenous system, is one of the important parameters to achieve desired concentration of drug in systemic circulation for desired (anticipated) pharmacological response. The major problem encountered with formulation development of new chemical entities as well as for the generic development is low aqueous solubility. It is seen that out of the total number of NCE (new chemical entities) developed, 40% seems to be practically insoluble in water. Thus solubility becomes the major challenge for a formulation scientist. For any drug to be absorbed it should be present in the solution form at the site of absorption. For enhancement of solubility there are various techniques that are used. These techniques include; Physical modifications techniques like media milling/ nanocrystal technology, cryogenic technology, supercritical fluid process, modification of the crystal habit, complexation, micellar technologies and chemical modifications. Other techniques like co-crystallization, co-solvency, hydrotrophy are used to increase the solubility of very soluble drugs like dolargin, loperamide, tubocurarine, doxorubicin, ibuprofen, griseofulvin, diazepam, naproxen, carbamazepine, nifedipine, phytosterol etc. Thus selection of solubility improving methods depends on drug property, site of absorption, and required dosage form characteristics.